Aromatic esters are important building blocks for various pharmaceuticals and agrochemicals, whereas phenyl esters are widely used in liquid crystals, photosensitizers and biologically active compounds. Aromatic amides are an important functional group of various natural products and designed pharmaceutical molecules. Some heterocyclic amides are potential CNS (central nervous system)-active compounds.
Traditionally, these esters were synthesized via reaction of the carboxylic acid with alcohols or phenols. Carbonylation of the aryl halides in the presence of an alcohol/phenol is an attractive alternative method that tolerates a wide range of substrates, thus demonstrating a great advantage for the synthesis of substituted aromatic esters and its derivatives. In this regard, various palladium-based catalytic systems, such as Pd(OAc)2, 10 PdCl2(PhCN)2 with ferrocenyl phosphine ligand, and Pd(OAc)2/PPh3 in the presence of an ionic liquid, have been explored for alkoxycarbonylation and phenoxycarbonylation reactions. A variety of palladium-based homogeneous catalytic systems, such as PdBr2(PPh3)2/PdCl2(PPh3)2, Pd(dppp)Cl2, palladium-1,3-bis(dicyclohexyl-phosphino)propane-H2BF4, 16 and Pd(OAc)2/xantphos catalytic system, were used for this reaction. Amino carbonylation using an ionic liquid and Pd (OAc)2/PPh3 was explored by kollar and co-workers. However, these methods are plagued with: (i) Less functional group tolerance due to acidic and basic reaction conditions (ii) use or liberation of inflammable, toxic and explosive CO gas (iii) Use of expensive phosphine ligands or NHC catalysts and (iv) Need of heavy transition metal like Pd. Therefore, the industrial applicability of these processes is limited by the inherent problem of catalyst separation from the product as the palladium residues in the product stream could be a serious issue in the pharmaceutical industry.
Article titled “Intramolecular carbonylation of vinyl halides to form methylene lactones” by M. F. Semmelhack et al. J. Org. Chem., 1981, 46 (8), pp 1723-1726 reports intramolecular carbonylation of vinyl halides to obtain methylene lactones with convenient nickel reagent and preliminary applications in a two-step cyclization-carbonylation procedure.
Article titled “Preference of 4-exo ring closure in copper-catalyzed intramolecular coupling of vinyl bromides with alcohols” by Y Fang et al. published in J. Am. Chem. Soc., 2007, 129, 8092-8093 reports intramolecular O-vinylation of γ-bromohomoallylic alcohols with 10 mol % of CuI as the catalyst and 20 mol % of 1,10-phenanthroline as the ligand in refluxing MeCN led to the convenient formation of the corresponding 2-methyleneoxetanes in good to excellent yields via a 4-exo ring closure. 4-exo cyclization is preferred over other modes of cyclization. The products 2-methyleneoxetanes are obtained by coupling reaction.
Article titled “Palladium-catalyzed carbonylation reactions of aryl halides and related compounds” by A Brennführer et al. published in Angew Chem Int Ed Engl., 2009; 48(23), 4114-33 reports the review summarizes recent work in the area of palladium-catalyzed carbonylation reactions of aryl halides and related compounds. Palladium-catalyzed carbonylation reactions of aromatic halides in the presence of various nucleophiles have undergone rapid development such that nowadays a plethora of palladium catalysts are available for different carbonylative transformations. The carboxylic acid derivatives, aldehydes, and ketones prepared in this way are important intermediates in the manufacture of dyes, pharmaceuticals, agrochemicals, and other industrial products.
Article titled “Mild and efficient copper-catalyzed cyanation of aryl iodides and bromides’ by H J Cristau et al. published in Chemistry, 2005 Apr. 8; 11(8): 2483-92 reports an efficient copper-catalyzed cyanation of aryl iodides and bromides. The system combines catalytic amounts of both copper salts and chelating ligands. The latter, which have potential nitrogen- and/or oxygen-binding sites, have never previously been used in this type of reaction. A protocol has been developed that enables the cyanation of aryl bromides through the copper-catalyzed in situ production of the corresponding aryl iodides using catalytic amounts of potassium iodide. Aryl nitriles are obtained in good yields and excellent selectivities in relatively mild conditions (110° C.) compared with the Rosenmund-von Braun cyanation reaction. Furthermore, the reaction is compatible with a wide range of functional groups including nitro and amino substituents.
Article titled “Copper-catalyzed domino halide exchange-cyanation of aryl bromides” by J Zanon et al. published in J. Am. Chem. Soc., 2003, 125, 2890-2891 reports an efficient, mild, and inexpensive copper-catalyzed domino halogen exchange-cyanation procedure for aryl bromides. The new method represents a significant improvement over the traditional Rosenmund-von Braun reaction: the use of catalytic amounts of copper and a polar solvent greatly simplifies the isolation and purification. In addition, the new method exhibits excellent functional group compatibility.
In the light of above, there is a need in the art to provide a simple, effective and unified process for production of carboxylic acid derivatives. Accordingly, the inventors have developed a high yielding and operationally simple carbonylation process for the synthesis of acid derivatives starting from aryl/vinyl/alkyl halides in a single step under neutral reaction conditions without the use of hazardous carbon monoxide. Considering cyanide to be isoelectronic with CO, the present inventors have preferred to choose NaCN as it is a cheap, robust, water soluble, easy to handle and does not produce any undesirable waste (unlike stoichiometric use of CuCN).